REST, Ageing, and AD - PowerPoint PPT Presentation

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REST, Ageing, and AD

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  1. REST, Ageing, and AD By: Josh radparvar General Meeting 1 Spring 2014 14 April 2014

  2. Outline What is REST? What should happen? REST and AD Neuroprotective properties of REST Rest, cognitive preservation, and longevity Beyond AD

  3. REST Repressor element 1-silencing transcription factor AKA neuron-restrictive silencer factor (NRSF) Represses genes that promote cell death and Alzheimer’s disease pathology

  4. http://en.wikipedia.org/wiki/RE1-silencing_transcription_factorhttp://en.wikipedia.org/wiki/RE1-silencing_transcription_factor

  5. Normal Ageing

  6. Normal Ageing vs MCI vs AD

  7. Neuroprotective Properties Cell Viability Pro-Apoptotic Gene Expression

  8. REST-deficient mice progressive age-related neurodegeneration REST is crucial for supporting viability in the ageing brain

  9. REST and Cognitive Preservation

  10. REST and Tau • Braakstages: classification used to measure neurofibrillary tangles • Stages I and II are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain • Stages III and IV when there is also involvement of limbic regions such as the hippocampus • Stages V and VI when there is extensive neocortical involvement

  11. REST and Cognitive Preservation • Nuclear REST levels in Prefrontal Cortex with neuropathological AD • Moderate/frequent plaques • Intermediate/high likelihood of AD by NIA-Regan criteria

  12. REST and Longevity • Significance maintained even after multivariate adjustments for cognitive test scores and indices of neuropathology

  13. “REST dysfunction may contribute to the pathogenesis of a number of different neurodegenerative disorders. In addition to AD, REST was also significantly depleted in frontotemporal dementia and dementia with Lewy bodies. In each of these disorders, REST was lost from the nucleus and appeared in autophagosomes…”

  14. References Adopted from: Lu, T., et al. (2014). REST and stress resistance in ageing and Alzheimer/'s disease. Nature, 507(7493), 448-454. doi:10.1038/nature13163